We are developing chemical approaches to the study of the molecular basis of steroid hormone action. The technique of photoaffinity labeling has been selected as the most appropriate method for attaching covalently a radiochemical label to the high-affinity binding protein for estradiol, found in the rat uterus. We have prepared several derivatives of estradiol, estrone, and hexestrol that bear photolabile diazo and azide functional groups, and we have devised procedures for assaying the degree to which these attach covalently to the binding site upon irradiation. Further synthetic efforts are being directed at the radiochemical synthesis of the most promising compounds we have already prepared and at the synthesis of new labeling reagents that should bind with higher affinity (having the attaching functions placed in the center of the molecule, leaving the oxygen functions at the extremities free) and that will be bearing new and different photoattaching functions. Further refinements in the assays for covalent attachment are proposed, and plans have been formulated for studying the covalently labeled binding proteins, when they have been prepared.